Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy
consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in
treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer
cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as
CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help find out if this
approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Lymphoma
Enrollment Eligibility
Inclusion Criteria:
- Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10%
CD30 expression by immunohistochemistry in the following subtypes (by local review):
nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular
T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell
lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic
intestinal T-cell lymphoma
- Patients with expression of CD30 in >= 10% of the tumor (based on local
immunohistochemistry review) regardless of histology will not be permitted
- Patients with a diagnosis of other PTCL subtype histologies other than those
specified in the inclusion criteria are excluded including large cell
transformation of mycosis fungoides
- Patients will be stratified by presence or absence of TFH phenotype (i.e.
diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of
pathology. Determination of TFH phenotype can be defined by expression of two or
more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by
immunohistochemistry
- Measurable disease as defined by the Lugano criteria
- No prior systemic therapy for lymphoma (excluding corticosteroids)
- Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 7 days prior to registration is required
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement
from lymphoma per investigator assessment; the first 12 patients on each arm of the
study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x
upper limit of normal (ULN)
* Except in subjects with documented liver involvement by lymphoma
- Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
- Total bilirubin =< 2.0 x ULN
* Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement
by lymphoma
- Archival tissue must be available for submission
- Patients known to have HTLV 1/2 are excluded
- Patients with known central nervous system involvement are excluded
- No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive)
are permitted if they are negative by polymerase chain reaction (PCR). Those who are
seropositive for hepatitis B and are negative for hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed
antiviral therapy. Those who have hepatitis C Ab positivity who have completed
curative therapy for hepatitis C with negative hepatitis C PCR are eligible
- Patients with history of HIV are eligible if they have an undetectable viral load for
at least 6 months
- No active uncontrolled systemic fungal, bacterial or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy and/or other treatment). Patients with
Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
- No concurrent malignancy requiring active therapy within the last 3 years with the
exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited
to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer.
Adjuvant hormonal therapy for cancer previously treated for curative intent is
permitted
- Patients must have documented left ventricular ejection fraction of >= 45%
- No significant active cardiac disease within the previous 6 months including:
- New York Heart Association (NYHA) class III or IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention; and/or
- Myocardial infarction
- No contraindication to any drug in the chemotherapy regimen, including neuropathy >=
grade 2
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this
study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days
prior to registration on the study. Chronic concomitant treatment with strong CYP3A4
inducers is not allowed. Patients must discontinue the drug 14 days prior to the start
of study treatment